Related Experiment Video
Updated: Dec 28, 2025
Utilizing High Resolution Ultrasound to Monitor Tumor Onset and Growth in Genetically Engineered Pancreatic Cancer Models
Published on: April 7, 2018
Monitoring Dual VEGF Inhibition in Human Pancreatic Tumor Xenografts With Dynamic Contrast-Enhanced Ultrasound
Michele Lamuraglia1, Guillaume Barrois2, Delphine Le Guillou-Buffello2
1Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale (LIB), AP-HP, Hôpital Beaujon, Paris, France.
Background:
Association of drugs acting against different antiangiogenic mechanisms may increase therapeutic effect and reduce resistance. Noninvasive monitoring of changes in the antiangiogenic response of individual tumors could guide selection and administration of drug combinations. Noninvasive detection of early therapeutic response during dual, vertical targeting of the vascular endothelial growth factor pathway was investigated in an ectopic subcutaneous xenograft model for human pancreatic tumor.
Methods:
Dynamic contrast-enhanced ultrasound 12 MHz was used to monitor tumor-bearing Naval Medical Research Institute mice beginning 15 days after tumor implantation. Mice received therapy from 15 to 29 days with sorafenib (N = 9), ziv-aflibercept (N = 11), combined antiangiogenic agents (N = 11), and placebo control (N = 14). Sorafenib (BAY 43-9006; Nexavar), a multikinase inhibitor acting on Raf kinase and receptor tyrosine kinases-including vascular endothelial growth factor receptors 2 and 3-was administered daily (60 mg/kg, per os). Ziv-aflibercept (ZALTRAP), a high-affinity ligand trap blocking the activity of vascular endothelial growth factor A, vascular endothelial growth factor B, and placental growth factor was administered twice per week (40 mg/kg, intraperitoneally).
Results:
Functional evaluation with dynamic contrast-enhanced ultrasound indicated stable tumor vascularization for the control group while revealing significant and sustained reduction after 1 day of therapy in the combined group (P = .007). There was no survival benefit or penalty due to drug combination. The functional progression-free survival assessed with dynamic contrast-enhanced ultrasound was significantly higher for the 3 treated groups; whereas, the progression-free survival based on tumor size did not discriminate therapeutic effect.
Conclusions:
Dynamic contrast-enhanced ultrasound, therefore, presents strong potential to monitor microvascular modifications during antiangiogenic therapy, a key role to monitoring antiangiogenic combining therapy to adapt dose range drug.
Insights
Combining antiangiogenic drugs shows promise for cancer therapy. Dynamic contrast-enhanced ultrasound effectively monitors treatment response, guiding drug combinations for better outcomes.
Area of Science:
- Oncology
- Radiology
- Pharmacology
Background:
- Combining antiangiogenic therapies may enhance efficacy and overcome resistance.
- Noninvasive monitoring is crucial for guiding combination antiangiogenic drug selection and administration.
- Investigated noninvasive detection of early therapeutic response in a human pancreatic tumor xenograft model targeting the vascular endothelial growth factor pathway.
Purpose of the Study:
- To investigate noninvasive monitoring of early therapeutic response during dual, vertical targeting of the vascular endothelial growth factor pathway.
- To evaluate the utility of dynamic contrast-enhanced ultrasound in assessing antiangiogenic therapy response.
- To guide the selection and administration of antiangiogenic drug combinations.
Main Methods:
- Utilized 12 MHz dynamic contrast-enhanced ultrasound to monitor tumor-bearing mice.
- Administered sorafenib (multikinase inhibitor) and ziv-aflibercept (VEGF pathway inhibitor) individually and in combination, alongside a placebo control.
- Therapy was administered from day 15 to 29 post-tumor implantation.
Main Results:
- Dynamic contrast-enhanced ultrasound revealed a significant and sustained reduction in tumor vascularization within 1 day of combination therapy (P = .007).
- Functional progression-free survival assessed by ultrasound was significantly higher in all treated groups compared to the control.
- Tumor size-based progression-free survival did not effectively discriminate therapeutic effects.
Conclusions:
- Dynamic contrast-enhanced ultrasound demonstrates significant potential for monitoring microvascular changes during antiangiogenic therapy.
- This technique can play a key role in monitoring combination antiangiogenic therapy to adapt drug dosing.
- Ultrasound monitoring can guide personalized treatment strategies in antiangiogenic therapy.
